- aminophylline is a complex of (theophylline and ethylenediamine) 

Source

Pneumoconioses

• causes by deposition of particles which elicit and inflammatory response.

Asbestosis	Silicosis	Berylliosis
Primary from mining; Secondary exposure from using in manufacturing	Sand blasting etc	Electronics manufacture
Fibrous form of Magneiusm Silicate	SiO2 crystals	?Beryllium
Two Forms: Chrysolite - white asbestos, serpentien fibers - less harmful. Crosydolite - blue asbestos, straight fibers, more harmful
Pleural plaques 20 to 30 years after exposure - most on rib associated surfaace of pleura Benign effusions Diffuse pleural thickening Mesotheliomas Bronchial Carcinomas
	SiO2 crystals persist cause necrosis of phagocytosing macrophages -> enzymes release -> lung damage. (cessation of exoposure doens't hald lung damage); Macrophage toxicity predisposes to post primary tuberculosis.
Lower lobe predilection	Upper lobe fibrosis with lymph nodes which can calcify	Upper lobe predilection.

Causes of dominant R wave in V1

#2016GM-APR/Q01
RVH, Right sided Heart, RBB, Posterior MI

• Normal in children and young adults
• Right Ventricular Hypertrophy (RVH)
  • Pulmonary Embolus
  • Persistence of infantile pattern
  • Left to right shunt
• Right Bundle Branch Block (RBBB)
• Posterior Myocardial Infarction (ST elevation in Leads V7, V8, V9)
• Wolff-Parkinson-White (WPW) Type A
• Incorrect lead placement (e.g. V1 and V3 reversed)
• Dextrocardia (right sided heart)
• Hypertrophic cardiomyopathy
• Dystrophy
  • Myotonic dystrophy
  • Duchenne Muscular dystrophy
    -Source

[!INFO] Summary

LBBB	RBBB
Always pathological	Can be benign
Causes LAD	No effect on axis
Affects MI diagnosis	No effect on MI diagnosis

• New onset LBBB is always pathological, never ignore!
  • Sgarbossa criteria are used in this case.
  • Mnemonic: Hypertrophy or dilation of LV can cause LBBB.
• Idiopathic fibrosis, digoxin toxicity, hyperkalemia
• Cardiac scarring - disrupts conduction system
• Cardiac infiltration - disrupts conduction system. (amyloidosis)
  • RBBB is frequently asymptomatic and in this case, there is no risk of adverse outcomes.
  • Acute cor pulmonae (pulmonary embolism) can also cause RBBB.

[!TIP] Mnemonic: It seems that increase in ventricular afterload can cause ipsilateral bundle branch blocks.
? cause of LAD in LBBB?
?is it because The counterbalancing effect of RV depolarization on the axis is lost as the RV depolarizes later??
Verapamil is a suitable alternative for adenosine if it it contraindicated.

[!INFO] AV nodal blocking drugs
Source: Harrison's
Mnemonic: AV nodal Blocking drugs : AVB -> Adenosine, verapamil, beta blockers (after trying vagal maneuvers)
(+? others)

[!INFO] Mnemonics:
Adenocarcinoma : Acchis
SQCs : Smokers
4. Diagnosis: By anti-P/Q-type voltage-gated calcium channel (VGCC) antibody testing and high frequency RNS (repetitive nerves stimulation)
5. Targeted therapy for symptomatic LEMS with 3,4-diaminopyridine is usually first line.
6. Refractory cases : immunosuppressants and plasma exchange.

• Tendency to fall increases osteoporosis risk
• Obesity reduces osteoporosis
• Thiazide diuretics raises calcium so it helps bone density.
• Hypophosphataemia causes osteoporosis
• Teriparatide (although it is a form of PTH) reduces osteoporosis. (activates more osteoblasts than osteoclasts)

[!TIP] Hypercalcemia: Abdominal groans, psychich moans and renal stones.

Comparison of ABPA, EGPA and Hypersensitivity pneumonitis

Allergic bronchopulmonary aspergillosis
[[passMedicine Summaries#Hypersensitivity pneumonitis (HP)|Hypersensitivity Pneumonitis]]

• 3 times more common in women
• most commonly diagnosed in people aged 20-40 years
  • Relapses are caused by acute inflammation causing myelin damage and conduction block.
• Demyelination has a prediliction of cervical spinal cord, optic nerves, corpus callosum, cerebellar connections of the brainstem. (contrast with [[HIV-AIDS#^13ac5c|PML]] where spinal cord and optic nerves are spared)
  • PML can be cause by reactivation of JC virus which in turn can be promoted by therapy with natalizumab!!. (which is used to treat MS)

• Cerebellar: charcot triad -> Scanning speech (i.e dysarthria), nystagmus and intention tremmor. Youtube (mnemonic: No taxes for disabled)
• Uhthoff phenomenon - symptoms worsen in high temperatures.
• Lhermitte's sign - Electrical shock sensation running down the back when neck is flexed.
  • Fingolimod - sphingosine receptor modulator

| Metformin | Biguanide | Insulin sensitiztion Reduce hepatic gluconeogenesis.It activates AMPK (AMP activated protein kinase) | GI side effects Lactic acidosis (risk in renal/liver/heart failure – contrindications) No weight gain May reduce apetite, STOP when eGFR < 30 | Reduced GI B12 absorption The usual first line agent, can be combined with other | Lower FBS by about 50 mg/dL Lowers HbA1C by about 1% |
Mechanism of action: Increases intracellular c-AMP potentiated insulin secretion.

• Malignancies

• "Antiphospholipid antibodies" is a collective term for several of antibodies including anti cardiolipin antibodies and lupus anticoagulant and anti-beta2 glycoprotein I.

After initial detection on the FBC, the investigation of choice is immunophenotyping by flow cytometry to reveal cell surface markers typical of CLL, including CD5, CD19 and CD20.

Background physiology of lymphocytes

Source-YouTube
Source-YouTube
Source-YouTube

• Different B cells are sensitive to different antigens.

• Binding of the pathogen to B cell receptors (which are membrane bound antibodies) causes B cell activation.

• But Activation of B cells also requires co-stimulation by (activated) TH cells. The B cell engulfs the pathogen via receptor mediated endocytosis and presents antigen on an MHC II molecule. A Th cell reactive to this antigen will arrive, bind and activate the B cell. (this makes B cells professional APCs)
  • To complicate things, b cells require two signals from the Th cell to become activated. There is also a less potent form of b cell activation - T cell independent activation which is dependent on B cell receptor crosslinking by antigents - but this method is less potent.
  • 
• After activation, B cells become effector cells or memory cells.
  • Effector cells renter the cell cycle and begin to proliferate and produces antibodies -> The antibody producing cells are called plasma cells
  • memory cells persist for memory.
• T cell also require activation and after activation they become effector and memory T cells.
• Th cells have CD4 receptors which bind to MHC Class II and get activated by APCs.
• Tc cells have CD8 receptors which bind to MCH Class I and get activated by 'all nucleated cells' which present an antigen.
• See [[2021 Basic Sciences July#HLA molecules|HLA Molecules]]
• After activation,
  • Effector Th cells -> activate B lymphocytes and secrete cytokines. ("alarm ringer") (one such cytokine is interferron gamma)
  • Effector Tc cells kill host cells.
  • Memory cells of both types persist.
• B cells can undergo activation and class switching.
  • T cell activation of B cells occurs in the lymph nodes.
  • naive B cells have membrane bound IgM and IgD.
  • First step after activation is somatic hypermutation. This generates B cells with various affinities for the same specific antigen. Low affinity B cells die and high affinity B cells survive.
  • The surviving high affinity B cells will undergo class witching.
  • once activated, they will produced IgG / M/ D etc. (rather than their naive state IgM). This is called isotype switching or class switching
  • Isotype switching is irreversible. It is done by altering DNA coding for the Fc region of antibodies.
  • Once class switching is done, the cell is called a plasma cell.
  • The type of antibody produced as a result of class witching depends on which cytokine was secreted by the activating T cell.
    • IL4 -> promotes IgG or IgE
    • TGF-beta -> IgG2b, IgA
    • IL5 -> IgA
    • IFN-gamma -> IgG2a or IgG3
  • Hyper IgM Syndrome: CD40 ligand signalling is defective; these individuals cannot class switch; they can only generate IgM. Individuals are immunocompromised.

Natural killer cells

• Are CD8+ T cells which do not have a TCR (T Cell receptor).
• They have receptors for MHC molecules. Stimulation of these receptors results in inhibition of killing.
• NK cells will kill any host cell that doesn't express MHC molecules.
• So any (host) cell that does not express adequate MHC molecules cannot inhibit NK cells and is killed by NK cells.
• 
• Source
• 
• Source

Chronic lymphocytic leukemia features

• Chronic lymphocytic leukemias are characterized by accumulation of mature B or T lymphocytes in the blood.
• This is manifested as chronic persistent lymphocytosis.
• Distinction between non-Hodgkin lymphoma and chronic leukemia is not rigid and depends on the proportion of disease present in soft tissue Vs. Blood.

GVHD can occur after allogenic haemotopoietic cell transplantation or with solid organs containing lymphoid tissue. (Bowel transplant was one example)
GVHD arises when immune cells transplanted from a non-identical donor graft into the recipient (host), recognize the host cells as "foreign," thereby initiating a graft-versus-host reaction.

    - **Dermatitis** - painful, pruritic rash.  (not vessicles like in the mnemonic) 
- ![RashOfGraftVsHostDisease.png](RashOfGraftVsHostDisease.png)

14. Progressive multifocal leukoencephalopathy (PML) ^13ac5c

#2016GM-OCT/Q29

• Pincu - few weeks to several months.
• Leishmaniasis causes suppurative granulomas
• Protozoan parasite.
  In SL, leishmaniasis is reported mainly in Anuradphapura, polonnaruwa, hambantota and Matara. The disease was began spreading locally in the 1990s. Incidence has been increasing rapidly in the past decade.
• In Sri Lanka, Leishmania donovani (usually associated with visceral leshmaniasis (VL)) causes cutaneous leishmaniasis (CL). This is termed dermotropism. However, it can cause VL as well.
• Phelbotomus argentipes is the main vector in SL although others are also present.
• In SL, Leishmania incidence is seasonal.

Leishmaniasis: spectrum of disease.

Leishmaniasis has a wide spectrum of disease

At one end of the spectrum, mucosal leishmaniasis (ML) and leishmaniasis recidivans (LR) are caused by oligoparasitic disease associated with a marked cellular immune response.
The center of the spectrum consists of localized cutaneous leishmaniasis (LCL), which is the most common clinical presentation.
At the opposite end of the spectrum, diffuse cutaneous leishmaniasis (DCL) is caused by polyparasitic disease with a predominance of parasitized macrophages and no granulomatous inflammation.

Cutaneous leishmaniasis

This is the commoner form in Sri Lanka.
Symptoms:

• lesions are NOT painful.
• Regional lymphadenopathy may be present.
• Satellite nodules can be present.
  Diagnosis:
• Suspect in a patient with chronic skin lesions! (i.e not in the acute stage)
• Diagnosis is by demonstration of the parasite in a clinical specimen (usually skin) by histology, culture, or molecular analysis via polymerase chain reaction (PCR)

Diffuse cutaneous

Musocal leishmaniasis

Visceral leishmaniasis

• "black fever" refers to the grayish skin colouration that develop probably due to cytokine dysregulation.

• Main reservoir in Asia is dogs and foxes. (mnemonic: Dogs itch)

  • 

• #hepatosplenomegaly with #lymphadenopathy (but lymphadenopathy isn't common)

• Commonest presentation is with abrupt onset fever with chills and rigors which then continues for weeks.

• Splenomegaly seen by second week followed by hepatomegaly.

• Lymphadenopathy is seem but is rare in the indian subcontinent.

• weight loss

• Pancytopaenia can lead to thrombocytopenia which causes epistaxis, petechiae, purpura or other bleeding.

• Complications: DIC or macrophage activation syndrome.

• Diagnosis: Identification of the organisms in aspirate of bone marrow or liver or spleen.

  • sensitivities: spleen (90%) -> Bone marrow -> lymph nodes.
  • Biopsy shows typical kineoplast in the parasite.
  • Also montenigro test (similar to mantoux test for TB) - but this test is negative in the active phase of the disease. It also remains positive for life so in endemic areas, 70% are positive.

• Other investigations:

  • pancytopaenia, hypoalbuminaemia, and hypergammaglobulinaemia.

• Treatment: pentavalent antimony salts (Sodium stibogluconate / melumine antimoniate) OR IV liposomal amphotericin B and IM paromomycin. Some patients develop post kalar-azar dermal leishmaniasis.

Post-kala-azar dermal leishmaniasis (PKDL) is a complication of visceral leishmaniasis (VL); it is characterised by a macular, maculopapular, and nodular rash in a patient who has recovered from VL and who is otherwise well.

• Mimics leprosy in appearance but there is no sensory loss.
• Perioral region is the earliest affected.
• Lymphadenopathy may be observed in East African VL but is rare outside this region.

• Based on this chart: primary FSGS seems more likely to cause nephrotic syndrome and secondary FSGS appears to be more likely to cause proteinuria.

2. Hypercoaulable states can occur, specially with membranous nephropathy.
3. Sepsis is a major cause of death due to loss of immunoglobulin -> pneumococcal infections
4. Lipid abnormalities -> increased cardiovascular risk.
5. ACEi / ARB are indicated for all patients with nephrotic range proteinuria.

• mnemonic: DAS-clones
  

4. ?monoclonal deposition disease (presents with nephrotic range proteinuria

• Majority are idiopathic.
• Infections like syphilis, TB, mycoplasma.

[!INFO] What "Effacement" means:
"Errasing, dissapearance". (like effacement of the cervix)

In this phenomenon, the normal interdigitated foot processes are finally reorganized into a broad flattened process like a paddle. The morphological process of the foot process effacement has not fully elucidated. Source

FSGS

• FSGS - Focal areas of mesangial collapse and sclerosis.
• Causes: Idiopathic, HIV infection, previous glomerular disease, massive obesity.
• In FSGS, disctintion between primary and secondary FSGS is important as treatment differs
• Clinical picture is ==more towards nephritic== in secondary FSGS.
• FSGS recurs in transplanted kidneys.
• Corresponding with the focal nature of the sclerosis, most of the affected glomeruli are at the level of the corticomedullary junction; so superficial biopsies can miss the affected glomeruli .
• 

FSGS is more likely with inflammatory conditions like SLE - PasTest

FSGS pathology:

Source

in embryonic mice, parietal epithelial cells can migrate to the visceral layer and replace damaged podocytes (Right) but in the older mice, such replacement can't occur and results in sclerosis. (left)

Source

Minimal change Vs. FSGS

[!TIP]
MCD and FSGS are like cousins; FSGS is the evil cousin.

• Haematuria is commoner in FSGS than in MCD.
• MCD shows selective protein loss -> i.e mainly albumin and not higher molecular weight proteins like immunoglobulins. FSGS shows non-selective proteinuria.
• FSGS shows poor response to corticosteroids.
• Higher percentage of FSGS patients go on to develop CKD (50%). (adults have worse prognosis)
• MCD and FSGS both show minimal / no immune deposits.
• FSGS : FSGS changes are visible on light microscopy. MCD: few changes visible on light microscopy.

c | Electron microscopy image showing subepithelial electron-dense deposits (spikes)(black arrows) and basement membrane material between the electron-dense deposits (white arrows; 4,800×).

• Subepithelial deposits, granular IgG deposition. Immunofluorescence patter: granular.
  • mnemonic: All the metals; silver stains can be used to delineate the histolgy of membranous nephropathy.
• About 1/3 have spontaneous remission. 40% go on to have CKD; proteinuria is often persistent even if there's no CKD.
• Non selective protein loss; (albumin + other proteins)
• Type 1: subendothelial immune complex deposition -> splitting of capillary basement membrane -> tramline appearance. (Mnemonic: "All aboard the proliferative train") -> Tramlines

• Myasthenia gravis is associated with thymomas. 40% of patients with Thymoma have MG.
• Thymoma is the commonest tumour of the anterior mediastinum and is diagnosed in the 50s and 60s. Thymomas can cause airway compression (SOB) and cardiac tamponade.
• 
  | Myasthenia gravis | Lambert eaton symdrome |
  | --------------------------------------- | ------------------------------------------------------------- |
  | anti AchR antibofy | Antibody against voltage gated calcium channel |
  | | [[Hypertension in pregnancy#^cd77f6|Lambert Eaton syndrome]] |
  | | |
  | Facial and eye muscles and 'moves down' | predominant proximal muscle weakness (esp. of hip girlde) |
  | | 1st line Rx: 3,4-diaminopyridine |
  | | Cranial nerve involvement less than in MG |

Common problems in geriatric medicine are

• Frailty - #2021GM-JUL/Q02, #2016GM-OCT/Q
• Sarcopenia: progressive, systemic muscle disorder which leads to loss of muscle fibers, in particular fast twitch fibers.

Falls

#2016GM-OCT/Q25

• Polypharmacy is also a risk factor for falls.

Right ventricular infarction

• Suspect and look for right ventricular infarction in all patients with inferior STEMI
  Suspect when:

• ST elevation in V1

• ST elevation in V1 and ST depression in V2 (highly specific for RV infarction)

• Isoelectric ST segment in V1 with marked ST depression in V2

• ST elevation in III > II (Lead III is more rightward facing than lead II and hence more sensitive to the injury current produced by the right ventricle)
  

• The "posterior wall" may not even exist. Source but it does for exam purposes.

- Isolated posterior wall STEMI is uncommon.
- Tall R waves in V1 and V2 are reciprocals of Q waves in the posterior wall.

Post MI prognosis

• cAMP - (which is generated by activation of adenylyl cyclase (the green AC in the diagram) )- activates protein kinases.
• Protein kinases like PKA activate many enzymes (and ion channels) which regulate cellular metabolism or myosin light chain kinase which is required for smooth muscle contraction. (Phosphorylation of myosin light chain kinase inactivates it causing smooth muscle relaxation).
• Key Point : PDE inhibitors raise cAMP levels.

Coeliac disease

BCD + PRSTUvW
Bacterial overgrowh, Coeliac disease, Dermatitis herpetiformis
Parasites, Resection, Sprue, Tropical Srpue, Uv = radiation, Whipples

• Prolamins are proteins which have high glutamine and proline content so they don't get digested by pepsin and pass into the intestine.
• Prolamins actually pass through the epithelium and undergo deamination by transglutaminase which makes them more immunogenic.
• CD4 T cells are stimulated and the resulting inflammation causes disease.
• interferon gamma is involved.
• the disease process results in crypt hyperplasia and villous atrophy.
• Increased risk of small bowel lymphoma.
• Malabsorption can cause iron deficiency and folate deficiency.

Symptoms

Complications

• Associated with autoimmune diseases: IBD, [[2022-November#Primary Biliary Cirrhosis / Primary Biliary Cholangitis|PBC]], ILD, CLCD, epilepsy. (Mnemonic: all acronyms)

• gold standard: small bowel biopsy. (Most commonly from duodenum but also from jejunum)
  • Patient needs to be on a gluten containing diet for 6 weeks before serologic or biopsy testing for the tests to yield positive results.
• Serology is very useful : endomysial (IgA ) and tissue transglutaminase antibodies.
• Tissue transglutaminase antibodies (IgA) are first line: NICE
• Anti-gliadin is not recommended.
• Anti-casein is found in some patients.

• Occurs particularly in young adult males, with a male to female ratio of 4:1 Source
• Vector: Culex quinquefasciatus (in SL) but also aedes species and anophelesSource

[!INFO] It takes 1 hour to process 1 unit

• Cryoglobulins are Immunoglobulins and / or complement components which precipitate reversibly in at temperatures below 37°C.
• Cryoglubulins can cause a systemic small to medium vessel vasculitis triggered by cryoglobulin containing immune complexes.
  • Ig bound to Fc portion of polyclonal IgG = (? like Rheumatoid factor which is IgM against Fc of IgG)
  • Type 2 - Monoclonal IgM is bound to IgG and polyclonal IgG; often associated with hepatitis C.(also seen in SLE and Sjogren's, Hep B, HIV etc - i.e chronic viral infections)
    • Glomerular disease is more common in type 2 than type 3. -> membranoproliferative glomerulonephritis
  • Type 3 - Polyclonal IgM is bound to IgG and polyclonal IgG;
  • Type 2 and Type 3 are referred to as mixed cryoglobulins. They are commonly associated with infections, autoimmune diseases, and lymphoproliferative disorders: Hep C is the commonest infective cause.
    eg; digital ischemia, livedo reticularis, skin necrosis, purpura (due to vasculitis) , Raynaud phenomemon - specially with cold temperatures.
    

• Mutations in CDH1 gene causing reduced levels of E-cadherin
• APC gene mutations (adenomatous polyposis coli)
  Gastric cancer has poor prognosis and new treatment modalities are needed.
  Distal cancer incidence as reduced greatly but proximal and GE cancer incidence has increased.
  Lauren classification:
• Intestinal type: Bulkly, glandular cancers: usually adenocarcinoma. Associated with chronic gastritis and metaplasia. This type of cancer is reducing in incidence.
• Diffuse type: infiltrative growth pattern, desmoplastic reaction gives rise to linitis plastica.
• Commonest type is adenocarcinoma comprising 90%.
• Carcinoid tumours:
  Gastrin, produced by G cells of the antral glands promotes growth of gastric adenocarcinoma through cholecystokinin-B receptors which are over expressed in this cancer.
  1. chronic administration of proton pump inhibitors,
  2. atrophic gastritis
• H pylori can cause chronic gastritis leading to metaplasia.
  Types of cancer associated with H. pylori:
• Gastric adenocarcinoma (both diffuse and intestinal types)
• MALToma
  • The stomach is the commonest site of MALT tumours. (mucosa associated lymphoid tissue tumours)
  • Normal stomach doesn't have significant lymphoid tissue but H-pylori infection leads to aggregation of lymphocytes in the lamina propria.
  • Lymphocyte activation leads to follicle formation -> somehow proceeds to MALToma
  • Maltoma: H pylori stimulates H pylori reactive T cells which drive B cell proliferation; The lymphomas are of B cell origin.
    • Early H pylori eradication "cures" the lymphoma.

• Cardiovascular: Mitral valve prolapse.
  • But also MR, TR, Aortic root dilation, aortic dissection
• Valvular dysfunction - MR and AR + coronary aneurysms

📑Management of PCKD

• Manage blood pressure with ACEi / ARB
• Restrict dietary sodium
• Higher fluid intake is recommended. (>3) -> prevents nephrolithiasis and suppresses ADH which may increase cyst growth.
• Tolvaptan - given for high risk patients; proven benefit. (because ADH promotes cellular proliferation). Slows progress of disease. ?does not induce regression? #2020GM-JUL/Q29

[!TIP] Mnemonic: Don't confuse with PSC - PBC has 'cirrhosis' in the name -> liver tissue is inolved -> interlobular bile ducts are involved.
#2016GM-OCT/Q30
enterohaemorrhagic (EHEC) (aka STEC - shiga toxin producing E coli)

But there are actually 5 types.

1. ETEC causes watery diarrhea in resource-limited settings and is commonly found in food and water in areas without adequate sanitation
2. EPEC (enteropathogenic) was the first E. coli pathotype identified as a causative agent of watery diarrhea primarily in infants and young children in resource-limited settings
3. EAEC (enteroaggregative) is a causative organism of acute and chronic watery diarrhea in resource-limited and resource-rich regions
4. EHEC/STEC produces Shiga-toxin and includes serotypes O157:H7, as well as others
5. EIEC-induced diarrheal illness is uncommon due

• Source

Hook worm

Necator americanus ("American murderer")
and ancylostoma ceylonicum

• The adult worms embed into the mucosa with the anterior part and live in the caecum and ascending colon, shedding thousands of eggs per day. Their lifespan is about 1 year.
• Commonly asymptomatic

Bradykinin

[!TIP] Mnemonic : BPH - bradykinin, prostaglandin and histamine act together.

• Bradykinin is peptide with a half life of 17 seconds!.
  • "Bradykinin makes blood vessels look like leaky barrel" - B for barrel and bradykinin
  • 
• potent vasodilator. -> accumulation causes angiooedema and possibly the dry cough of ACEi therapy.
• Broken down by BOTH
  • ACE and
  • neprilysin.
• See [[ARNIMechanism.png]]
  
• C1 esterase is a complement activation inhibitor. (Also called C1-INH for inhibitor)
• Defieciency of C1 esterase causes unchecked activation of C1, C2 and C4. (i.e classical pathway)
• This causes activation of kallikrein which causes increased production of bradykinin --> angiooedema.
• Low C2 and C4 levels are seen in hereditary angioedema.
• Serum C4 is the most reliable and widely used screening tool
• Treatment: plasma derived C1 inhibitor. Fresh frozen plasma (FFP) if this is not available

- They are also some of the oldest antiepileptics. Newer drugs have better pharmacokinetics. 
- The narrow spectrum AEDs mostly work for specific types of seizures (such as focal, absence, **or** myoclonic seizures). 
- Broad spectrum AEDs additionally have some effectiveness for a *wide variety of seizures* (focal **plus** absence myoclonic seizures).

Source
- Mnemonic: cOllECtIvE (COLLECTIVE IS SIMILAR TO 'BROADLY') (LeCo-VoLT)

• Valproate, lamotrigine and levetiracetam are newer antiepileptic drugs so they have broader spectrum than the older ones. These 3 are active against both primary and secondary generalized epilepsy. (secondary generalized means "Focal to bilateral tonic-clonic seizure")
• Mnemonic: VLL
• Valproate is good for almost everything, including absence, myotonic, myoclonic, partial, secondary generalized. However, valproate should be avoided in females of child bearing age.
• Spectrum of lamotrigine is similar but it can worsen myoclonic seizures.
• Passmedicine: lamotrigine and levetiracetam are used for focal seizures.
• Levetiracetam: Drug of choice for partial and / or secondary generalized seizures. Non sedating.

Anxiety

• Antidepressants, SSRIs and SNRIs in particular, are considered first-line therapies for GAD and PD because they are effective and generally well tolerated.Source

If > 8 hours since ingection, NAC is given rather than methionine.

[!INFO] Paracetamol
1,4,8,16
Gastric lavage 1 hour.
Activated charcoal 4 hours. Levels also at 4 hours.
Before 8 hour, methionine can be given and is as effective as NAC.
After 8 hours, give NAC.
Liver damange unlikely if NAC started within 8 hours.

Criteria for liver transplantation

King's College Hospital criteria for liver transplantation (paracetamol liver failure)

• Arterial pH < 7.3, 24 hours after ingestion

• or all of the following:

  • prothrombin time > 100 seconds
  • creatinine > 300 µmol/l
  • grade III or IV encephalopathy
    ECG: widened QRS, AV block, ventricular arrhythmias

• respiratory alkalosis – hyperventilation (in early stages with high salicylate levels)

• metabolic acidosis – lactate
  hypokalemia
  Management

• supportive

• alkaline diuresis was used earlier

almost identical to cinchonism (quinine toxicity).

• visual impairment favours a diagnosis of quinine toxicity
• In terms of management however, whereas aspirin can be cleared from overdose victims by haemofiltration, quinine cannot be extracted easily by extracorporeal methods. Central nervous symptoms such as tinnitus, deafness and visual defects which may occur with aspirin are usually transient whereas quinine leaves permanent neural damage, if the patient survives.

Non alcoholic fatty liver disease (NASH)/(NALFD)

Hypersensitivity pneumonitis (HP)

Source

• Caused by sensitization and reexposure to allergens, often associated with occupations.
• Clinical features are cough, dyspnoea, fatigue
• Most commonly associated with farming, birds and water contamination.
• eg: farmers lung, Bird fancier's lung, cheese washer's lung, hot tub lung, wine grower's lung.
• HP is caused by a Type IV hypersensitivity reaction.
• Repeated exposure to antigen in genetically susceptible people leads to acute neutrophilic and mononuclear alveolitis, followed by interstitial lymphocytic infiltration and granulomatous reaction.
• Contrast with
  • pneumoconioses where the damage is caused by inflammation resulting from particle deposition in the lung.
  • Organic dust toxic syndrome / silo fillers lung - where toxins in the inhaled particles cause lung damage.
  • Occupational asthma - but OA has airflow obstruction, airway eosinophilia, and different triggering antigens.

Symptoms

Investigations
CXR - Non specific.
HRCT - profuse, poorly defined centrilobular micronodules is the most characteristic findings. Fibrosis in Chronic HP.
BAL - Lymphocytosis with CD8+ predominance. (lymphocytosis with CD4+ predominant is seen in sarcoidosis)

Treatment:

• Acute: Steroids + antigen avoidance-> Completely reversible.
• Chronic: Longer term steroids; fibrosis is irreversible.